Pdx1 promotes ESC differentiation into insulin producing cells

Abstract

Type 1 diabetes can be treated by islet transplantation. However, acute shortage of organ donors, lifelong immunosuppression and chronic graft rejection are the current major limitations. Embryonic stem cells (ESC) offer a novel approach towards developing a treatment for type 1 diabetes. We hypothesized that reprogramming of the ESC using a pancreatic β cell specific transcription factor Pdx1 will lead to their enhanced differentiation into insulin producing cells (IPCs). A double stable ESC line R1 Pdx1AcGFP RIP Luc simultaneously co‐expressing EF1α promoter driven Pdx1AcGFP and rat insulin promoter (RIP) driven luciferase was generated. Undifferentiated R1 Pdx1AcGFP RIP Luc ESC line expressed Oct4, Nanog, Pdx1 and AcGFP. The R1 Pdx1AcGFP RIP Luc ESC line was subjected to Activin A treatment to generate definitive endoderm (DE) cells which were characterized by CXCR4 expression on the cell surface. The selectively enriched CXCR4+ DE cells were directly infused into streptozotocin induced diabetic mice which led to their in vivo homing into the pancreas, differentiation into IPCs and sustained correction of hyperglycemia. Real‐time non‐invasive bioluminescence imaging was used to monitor the long term in vivo fate of the transplanted IPCs. In conclusion, R1 Pdx1AcGFP RIP Luc‐derived IPCs offer a novel approach for the treatment of type 1 diabetes.